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Hepatic, lipid and genetic factors associated with obesity: crosstalk with alcohol dependence?

ABSTRACT: OBJECTIVES:Alcohol dependence represents a leading cause of mortality and morbidity. Understanding the variables that contribute to this diagnosis and its severity is critical. An overlap between factors that may predispose people to become obese and those that may increase the risk of alcohol dependence may exist. However, data in the literature are not conclusive. Therefore, this study aimed to identify the association between alcohol dependence and obesity-related factors, including biochemical and genetic factors. METHODS:In a case-control study with 829 participants, factors involved with metabolism and obesity were assessed, including biochemical lipid and liver markers, and the fat mass and obesity-associated (FTO) single nucleotide polymorphism (SNP) rs8050136. RESULTS:Increased triglycerides, having one or two minor A alleles for rs8050136 and being a smoker were associated with increased risk of alcohol dependence, while increased low-density lipoprotein cholesterol was associated with decreased risk. In addition, having abnormal gamma-glutamyl transferase and being female were factors associated with an increased severity of alcohol dependence. CONCLUSIONS:Our preliminary findings suggest a link between alcohol dependence and obesity-related biochemical and genetic factors. Future studies are needed to better understand if these factors may play a predictive role and/or may act as biomarkers for treatment response.

SUBMITTER: Goodyear K

PROVIDER: S-EPMC5382351 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Hepatic, lipid and genetic factors associated with obesity: crosstalk with alcohol dependence?

Goodyear Kimberly K Lee Mary R MR Schwandt Melanie L ML Hodgkinson Colin A CA Leggio Lorenzo L

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 20161201 2

<h4>Objectives</h4>Alcohol dependence represents a leading cause of mortality and morbidity. Understanding the variables that contribute to this diagnosis and its severity is critical. An overlap between factors that may predispose people to become obese and those that may increase the risk of alcohol dependence may exist. However, data in the literature are not conclusive. Therefore, this study aimed to identify the association between alcohol dependence and obesity-related factors, including b ...[more]

PMID: 27905213

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Project description:ImportanceAlcohol dependence (AD) and major depression (MD) are leading causes of disability that often co-occur. Genetic epidemiologic data have shown that AD and MD share a common possible genetic cause. The molecular nature of this shared genetic basis is poorly understood.ObjectivesTo detect genetic risk variants for comorbid AD and MD and to determine whether polygenic risk alleles are shared with neuropsychiatric traits or subcortical brain volumes.Design, setting, and participantsThis genome-wide association study analyzed criterion counts of comorbid AD and MD in African American and European American data sets collected as part of the Yale-Penn study of the genetics of drug and alcohol dependence from February 14, 1999, to January 13, 2015. After excluding participants never exposed to alcohol or with missing information for any diagnostic criterion, genome-wide association studies were performed on 2 samples (the Yale-Penn 1 and Yale-Penn 2 samples) totaling 4653 African American participants and 3169 European American participants (analyzed separately). Tests were performed to determine whether polygenic risk scores derived from potentially related traits in European American participants could be used to estimate comorbid AD and MD.Main outcomes and measuresComorbid criterion counts (ranging from 0 to 14) for AD (7 criteria) and MD (9 criteria, scaled to 7) as defined by the DSM-IV.ResultsOf the 7822 participants (3342 women and 4480 men; mean [SD] age, 40.1 [10.7] years), the median comorbid criterion count was 6.2 (interquartile range, 2.3-10.9). Under the linear regression model, rs139438618 at the semaphorin 3A (SEMA3A [OMIM 603961]) locus was significantly associated with AD and MD comorbidity in African American participants in the Yale-Penn 1 sample (β = 0.89; 95% CI, 0.57-1.20; P = 2.76 × 10-8). In the independent Yale-Penn 2 sample, the association was also significant (β = 0.83; 95% CI, 0.39-1.28; P = 2.06 × 10-4). Meta-analysis of the 2 samples yielded a more robust association (β = 0.87; 95% CI, 0.61-1.12; P = 2.41 × 10-11). There was no significant association identified in European American participants. Analyses of polygenic risk scores showed that individuals with a higher risk of neuroticism (β = 1.01; 95% CI, 0.50-1.52) or depressive symptoms (β = 0.87; 95% CI, 0.32-1.42) and a lower level of subjective well-being (β = -0.94; 95% CI, -1.46 to -0.42) and educational attainment (β = -1.00, 95% CI, -1.57 to -0.44) had a higher level of AD and MD comorbidity, while larger intracranial (β = 1.07; 95% CI, 0.50 to 1.64) and smaller putamen volumes (β = -1.16; 95% CI, -1.86 to -0.46) were associated with higher risks of AD and MD comorbidity.Conclusions and relevanceSEMA3A variation is significantly and replicably associated with comorbid AD and MD in African American participants. Analyses of polygenic risk scores identified pleiotropy with neuropsychiatric traits and brain volumes. Further studies are warranted to understand the biological and genetic mechanisms of this comorbidity, which could facilitate development of medications and other treatments for comorbid AD and MD.

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Hepatic, lipid and genetic factors associated with obesity: crosstalk with alcohol dependence?

Publications

Hepatic, lipid and genetic factors associated with obesity: crosstalk with alcohol dependence?

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